By Marti Webb Slay
The summer of 2023 brought some important improvements in diagnostic screening and treatment options for Alzheimer’s disease. David S. Geldmacher MD, Director of the Division of Memory Disorders and Behavioral Neurology at UAB, called the developments a revolution.
“A blood-based biomarker screening test that came out this summer is a game changer,” Geldmacher said. “Since Alzheimer’s was identified in 1906, the definitive diagnosis has eluded us. Only in the last several years have PET scans been able to demonstrate the presence of the amyloid plaque in the brain. And even that is not enough to tell us that Alzheimer’s disease is definitely the cause of memory loss because many of us will accumulate some plaque over the course of our lifetime and that, by itself, may not be particularly toxic. Now the blood-based biomarkers allow us to identify the presence of the abnormal Alzheimer protein (amyloid beta) and also identify evidence it is causing damage to the brain.”
PET scans and spinal fluid biomarkers can support an Alzheimer’s diagnosis, but they are difficult to access. “There are only a few PET scanners in the state, and not many physicians want to do spinal taps,” Geldmacher said. The blood-based biomarker screen, which is commercially available and can be drawn at local lab facilities, can indicate the probability of whether PET scan, which is a more definitive test, will identify Alzheimer’s changes in the brain.
“Now physicians have the opportunity to really understand the biological relationship between blood biomarkers and the likelihood that Alzheimer’s is causing memory symptoms,” he said. “For patients, this means that if you forgot your car keys or misplaced your glasses, and the biomarker screen is negative, then Alzheimer’s disease is almost certainly not the cause of your symptoms. And that’s good news to have.”
While the screening test has proven to be effective, it is not yet covered by most insurance, including Medicare. “The downside is the clinical utility and cost effectiveness has not yet been demonstrated to Medicare to their satisfaction,” Geldmacher said. “So for now, Medicare and other insurers don’t pay for this testing. It is out of pocket, and the cost ranges from hundreds of dollars up to several thousand. Many people find it critically important to know whether or not they have Alzheimer’s changes in their brain so they are willing to make that investment.”
New medications are the second aspect of the Alzheimer’s summer 2023 revolution. In July, the FDA granted full approval to Leqembi®, and Medicare extended coverage for the drug. Also in July, JAMA published a successful Phase III trial of donanemab.
These new drugs are important because while the older drugs out there can make brain cells work better, they don’t alter the cells’ survival. This new medicine reduces the rates of brain cell death, so they slow the progression whereas the old drugs simply delay the progression. Lecanemab (Leqembi) slows the clinical progression of the disease by 25 to 35 percent. This can add years of independence for someone whose symptoms are mild.
“The challenge will be to distinguish whether the disease progression is just delayed or actually slowed down, because that can’t be demonstrated by memory tests in the office,” Geldmacher said. “The magnitude of effect for the two medicines is pretty similar for the first year. At some point, probably at six, 12 or 18 months, we’ll redo the PET scan. If the amyloid is gone from the brain, then we’ll know the drug has done its job and we’ll stop using it.
“The trial of donanemab provides hope that the drug can, in fact, be discontinued at some point. At six months of treatment, a third of the people had their amyloid gone. At 18 months of treatment, more than 80 percent had their amyloid gone. So now clinicians thinking that we probably don’t need to give most patients more than 18 months of treatment. Or we can check, and if the amyloid is gone, we’ll stop the drug. Data from two different medications on the rate of re-accumulation of amyloid after stopping the drugs suggests that the amyloid will still be below the threshold of treatment for five to eight years after stopping the medicine.”
Cost will be one of the big questions for the new medicines. While one of the old medicines, Aricept, costs about $100 per month, Leqembi costs over $2000 per month. In addition, it must be administered by infusion every two weeks. “This fall, Leqembi announced preliminary results for a subcutaneous injection, so they are continuing to develop simpler means to administer it,” Geldmacher said. “We don’t yet know if it would be home administration, like with insulin for diabetes patients.”
Although many questions still remain about the cost-effectiveness of both the screening test and new medications, as well as the convenience of administering the new drugs, it is clear that these new developments will provide many answers in the treatment of Alzheimer’s disease.
“Even if this is not something we are using 20 years from now, it’s something that will inform what we should be working on,” Geldmacher said. “In the end, we are trying to get the right drug to the right people at the right time. And for the moment, that involves some up-front costs, but we expect to save a lot of back end costs for people too.”